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Start UPTRAVI®

Starting Your PAH Patients on UPTRAVI®—Setting Treatment Goals and Expectations

When you decide to start your patient on treatment with UPTRAVI®, it’s important to set goals and expectations with them.

Before starting UPTRAVI®:

  • Ensure patients know that dose adjustment (titration) is necessary and temporary1
  • Inform patients and caregivers of ways to MANAGE SIDE EFFECTS before patients start treatment
  • Ask patients what’s most important to them in their treatment with UPTRAVI®. Let them know what to expect and who to contact to help
    them and their loved ones be prepared for treatment
  • Encourage patients to TRACK HOW THEY ARE FEELING during treatment and to contact you if they have questions about any side effects

UPTRAVI® Dose Adjustment Phase—Helps Meet Individual Patient Needs1

UPTRAVI® dosing is unique to each patient based on how their body responds and adjusts to treatment. The dose adjustment phase is how you find your patient’s personal maintenance dose.

Titrating UPTRAVI® doses mobile graphic
Tablet not shown at actual size.

*Once daily for patients with moderate hepatic impairment (Child-Pugh class B) and co-administration with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox, and teriflunomide). Increase in increments of 200 mcg once daily at weekly intervals.

Recommended starting dose is 200 mcg twice daily. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.

  • If a dose of UPTRAVI® is missed, patients should take the missed dose as soon as possible unless the next dose is within the next 6 hours
  • If treatment is missed for 3 days or more, restart UPTRAVI® at a lower dose and then retitrate
The goal is to reach the dose that’s right for each patient, not necessarily to reach 1600 mcg

After the dose adjustment phase1

Once each patient reaches their personal dose (maintenance), a single-tablet equivalent is prescribed BID. There are 8 different single-tablet strengths of UPTRAVI®, each a unique color.

UPTRAVI® OFFERS A RANGE OF DOSE STRENGTHS TO ACCOMMODATE EACH PATIENT’s personal MAINTENANCE dose

pill-2
200 mcg Light yellow
pill-4
400 mcg Red
pill-6
600 mcg Light violet
pill-8
800 mcg Green
pill-10
1000 mcg Orange
pill-12
1200 mcg Dark violet
pill-14
1400 mcg Dark yellow
pill-16
1600 mcg Brown
Comparison of pill and dime
Size shown in relation to a dime for proportional comparison. Tablet not shown at actual size. Actual tablet size is 7 mm.

TREATMENT EFFECT OF UPTRAVI® WAS SIMILAR, REGARDLESS OF THE PERSONAL MAINTENANCE DOSE ACHIEVED1-3

Time to first disease progression event in GRIPHON by dose group
Percent of patients without an event across UPTRAVI® low-dose, medium-dose, high-dose, and placebo groups mobile curve

Efficacy by dose group†:

  • 40%
    RISK REDUCTION
    (low dose:
    200 mcg to 400 mcg)
    HR 0.60 (95% CI: 0.41, 0.88)
  • 47%
    RISK REDUCTION
    (medium dose:
    600 mcg to 1000 mcg)
    HR 0.53 (95% CI: 0.38, 0.72)
  • 36%
    RISK REDUCTION
    (high dose:
    1200 mcg to 1600 mcg)
    HR 0.64 (95% CI: 0.49, 0.82)

UPTRAVI® doses were achieved across the 3 prespecified groups in the GRIPHON trial‡

  • 200 mcg to 400 mcg BID (low dose): 23% of patients (n=133)
  • 600 mcg to 1000 mcg BID (medium dose): 31% of patients (n=179)
  • 1200 mcg to 1600 mcg BID (high dose): 43% of patients (n=246)

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI® is contraindicated.

Hypersensitivity to the active substance or to any of the excipients is contraindicated.

WARNINGS AND PRECAUTIONS

Pulmonary Edema with Pulmonary Veno-Occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI®.

ADVERSE REACTIONS

Adverse reactions more frequent compared to placebo (≥3%) seen with UPTRAVI® Tablets are headache (65% vs 32%), diarrhea (42% vs 18%), jaw pain (26% vs 6%), nausea (33% vs 18%), myalgia (16% vs 6%), vomiting (18% vs 9%), pain in extremity (17% vs 8%), flushing (12% vs 5%), arthralgia (11% vs 8%), anemia (8% vs 5%), decreased appetite (6% vs 3%), and rash (11% vs 8%).

These adverse reactions are more frequent during the dose titration phase.

Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI® Tablets and in none of the patients on placebo.

DRUG INTERACTIONS

CYP2C8 Inhibitors

Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant use of UPTRAVI® with strong inhibitors of CYP2C8 is contraindicated.

Concomitant administration of UPTRAVI® with clopidogrel, a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag and increased the exposure to the active metabolite by approximately 2.7–fold. Reduce the dosing of UPTRAVI® to once daily in patients on a moderate CYP2C8 inhibitor.

CYP2C8 Inducers

Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to the active metabolite. Increase UPTRAVI® dose, up to twice, when co-administered with rifampin. Reduce UPTRAVI® when rifampin is stopped.

DOSAGE AND ADMINISTRATION

Recommended Dosage

Recommended starting dose is 200 mcg twice daily for UPTRAVI® Tablets. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.

Patients With Hepatic Impairment

For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI® Tablets is 200 mcg once daily. Increase by 200 mcg once daily at weekly intervals, as tolerated. Avoid use of UPTRAVI® in patients with severe hepatic impairment (Child-Pugh class C).

Co-administration With Moderate CYP2C8 Inhibitors

When co-administered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI® to once daily.

Dosage Strengths

UPTRAVI® tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.

Additional Important Safety Information for UPTRAVI® IV

Use UPTRAVI® for injection in patients who are temporarily unable to take oral therapy.

Administer UPTRAVI® for injection twice daily by intravenous infusion at a dose that corresponds to the patient’s current dose of UPTRAVI® Tablets (see Table 1 in full Prescribing Information). Administer UPTRAVI® for injection as an 80-minute intravenous infusion.

Adverse Reactions: Infusion-site reactions (infusion-site erythema/redness, pain and swelling) were reported with UPTRAVI® for injection.

INDICATION

UPTRAVI® (selexipag) is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness of UPTRAVI® Tablets was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.

Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%).

Please see full Prescribing Information for UPTRAVI®.

cp-126160v5

†Not adjusted for multiplicity.

‡In the UPTRAVI® group, 14 patients discontinued the 200 mcg twice-daily dosage during the dose adjustment phase and 1 patient received doses different from the per protocol dosing; all 15 were assigned to 0 mcg and are not reported here.

BID=twice daily; CI=confidence interval; GRIPHON=Prostacyclin (PGI2) Receptor Agonist In Pulmonary Arterial HypertensiON; HR=hazard ratio.

References: 1. UPTRAVI® (selexipag) full Prescribing Information. Actelion Pharmaceuticals US, Inc. 2. Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373:2522-2533. 3. Sitbon O, Channick R, Chin KM, et al. Supplemental appendix to: Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373:2522-2533.